Bone loss occurs in surgical treatment procedures such as orthopedic and dental surgery, traumatic injuries, or tumor removal, and implants and substitutes are widely used to restore areas of bone loss. In this regard, for successful in vivo repair, it is important to use a material capable of bearing loads of hard tissues and stimulating osteoprogenitor cells to induce bone regeneration (Kokubo, T, Kim, H-M, Kawashita, M, 2003. Biomaterials 24: 2161-2175).
Silica has been reported to play an important role in bone formation, because it has supporting and protecting functions, prevents penetration of connective tissue in the bone loss area, and stimulates expressions of osteogenic differentiation-related genes and cell proliferation (Wong Po Foo, C, Huang, J, Kaplan, D L, 2004. Trends Biotechnol. 22: 577-585).
With recent development of nanotechnology, many studies have been conducted to develop materials including silica-based nanoparticles, and they have been reported to have high bone regeneration effects (Bosetti, M, Cannas, M, 2005. Biomaterials 26: 3873-3879). For this reason, various medical biomaterials such as nanoscale silica-based coatings for implants or bone substitutes, catheters, dental materials and medical instrument may be used.
However, the silica nanoparticles have disadvantages that they are easily detached from the material surface when a widely used physical/chemical deposition method is used, and they require acidic or basic conditions and various chemical additives and thus are accompanied by a potential risk of toxicity when a sol-gel precipitation method is used.
Further, a lithography method is problematic in that this method is limited to the target surface on which silica is formed, and is not suitable for in vivo environments (Caruso, R A, Antonietti, M, 2001. Chem. Mater. 13: 3272-3282). For this reason, there is an urgent need for a surface immobilization strategy which is biocompatible and effective for immobilization of silica nanoparticles on various surfaces.
Many organisms produce siliceous structures such as frustules in diatoms, spicules in sponges, and silica phytoliths in higher plants, which confer support and protection. Formation of the siliceous structures occurs in the organisms by particular proteins such as silicatein, silaffin, etc., and under environments similar to the biological conditions such as neutral pH, room temperature, etc. (Fan, T X, Chow, S K, Zhang, D, 2009, Prog. Mater. Sci. 54: 542-659).
In particular, R5 peptide which is a silica-binding peptide derived from a silaffin protein of the diatoms Cylindrotheca fusiformis induces and regulates silica formation under environments similar to the biological conditions so as to form silica nanoparticles (Sumper, M, Kroger, N, 2004, J. Mater. Chem. 14: 2059-2065).
Meanwhile, mussels, one of marine organisms, produce and secrete adhesive proteins that tightly attach themselves to wet solid surfaces such as underwater rocks, and thus they are not influenced by wave impact or buoyancy of seawater. Mussel adhesive proteins are known as a strong natural adhesive, and they exhibit about two times higher tensile strength than epoxy resin while having flexibility, compared to chemically synthesized adhesive (Lee, B P, Messersmith, P B, Israelachivili, J N, Waite, J H, 2011. Annu. Rev. Mater. Res. 41: 99-132).
Further, mussel adhesive proteins are able to adhere to various surfaces such as plastics, glass, metal, Teflon and biomaterials, and the like, and allow adhesion on wet surface within a few seconds, which remains an unsolved problem in development of chemical adhesives (Lee, B P, Messersmith, P B, Israelachivili, J N, Waite, J H, 2011. Annu. Rev. Mater. Res. 41: 99-132).
To obtain 1 gram of the adhesive material naturally extracted from mussels, however, about ten thousand of mussels are required. Therefore, despite very excellent physical properties of the mussel adhesive protein, there are many restrictions in industrial applications of the naturally extracted mussel adhesive proteins. As an alternative, a genetic recombination technology has been employed to mass-produce mussel adhesive proteins including Mefp (Mytilus edulis foot protein)-1, Mgfp (Mytilus galloprovincialis foot protein)-1, Mcfp (Mytilus coruscus foot protein)-1, Mefp-2, Mefp-3, Mgfp-3 and Mgfp-5, etc. (Cha, H J, Hwang, D S, Lim, S, 2008. Biotechnol. J. 3: 631-638; Hwang, D S, Yoo, H J, Jun, J H, Moon, W K, Cha, H J, 2004. Appl. Environ. Microbiol. 70: 3352-3359).
Mass-production of these recombinant mussel adhesive proteins is possible by using an E. coli expression vector, and these proteins are found to maintain adhesive strength of the existing mussel adhesive proteins (Hwang, D S, Gim, Y, Yoo, H J, Cha, H J, 2007. Biomaterials 28: 3560-3568; Cha, H J, Hwang, D S, Lim, S, White, J D, Matos-Perez, C R, Wilker, J J, 2009. Biofouling 25: 99-107).
However, there have been no reports about a mussel-inspired adhesive material, which is prepared by incorporating the recombinant mussel adhesive proteins having adhesion strength to various surfaces while being produced in a large amount with the silica nanoparticles.